Elevated levels of plasma homocyst(e)ine (H(e)) is an independent risk factor for arterial occlusive disease. It has been hypothesized that H(e) may contribute to this risk by inhibiting endothelial function. To test this hypothesis, the interaction between plasma H(e) levels and flow-mediated (endothelium-dependent) brachial artery vasodilation was tested in 25 men and women with coronary artery disease. Brachial artery dilation was measured ultrasonically before and after 5 minutes of proximal forearm arterial occlusion. Longitudinal arterial images were obtained with a 5.7 MHZ linear array probe; flow was quantified with simultaneous Doppler velocity determinations. Arterial diameters and blood velocity were determined in digitalized scans using computerized image analysis software. Plasma H(e) concentrations (range 7.52 - 68.39 nmol/mL) were inversely related to the magnitude of brachial artery flow-mediated vasodilation (r = 0.46, p = 0.02). Subjects in the highest compared to lowest tertiles of plasma H(e) (median 16.26 vs. 8.29 nmol/mL) demonstrated significantly less flow-mediated vasodilation (relative dilation - 1.1% vs. q5.4%, p = 0.016). The frequency of paradoxical flow-mediated vasoconstriction was greatest among subjects in the highest compared to lowest tertiles of H(e) (62.5% vs. 12.5%, odds ratio 11.7). In conclusion, these preliminary data suggest that elevated plasma concentrations of H(e) are associated with abnormal brachial artery flow-mediated (endothelium-dependent) vasodilation in subjects with coronary artery disease.